6533b85dfe1ef96bd12be77f
RESEARCH PRODUCT
Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling.
Isabel FariñasAriadna LagunaMaria L. ArbonésMireia MorenoSacri R. FerrónEva PorlanNatividad PozoCristina FillatPilar SánchezSergi ArandaSusana De La Lunasubject
Cell divisionMitosisProtein Serine-Threonine KinasesMiceNeural Stem CellsCell MovementGeneticsSubependymal zoneAnimalsHumansEpidermal growth factor receptorPhosphorylationMitosisProgenitorAdaptor Proteins Signal TransducingbiologyProtein StabilityIntracellular Signaling Peptides and ProteinsMembrane ProteinsCell BiologyProtein-Tyrosine KinasesSTEMCELLNeural stem cellCell biologyErbB ReceptorsStem cell divisionCancer researchbiology.proteinMolecular MedicineSignal transductionCell DivisionSignal Transductiondescription
SummaryStem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ). We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a dosage is required to sustain EGFR in the two daughters of a symmetrically dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during mitosis, and biochemical analyses indicate that it prevents endocytosis-mediated degradation of EGFR by a mechanism that requires phosphorylation of the EGFR signaling modulator Sprouty2. Finally, Dyrk1a heterozygous NSCs exhibit defects in self-renewal, EGF-dependent cell-fate decisions, and long-term persistence in vivo, suggesting that symmetrical divisions play a role in the maintenance of the SEZ reservoir.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-09-01 | Cell stem cell |